Less than 10 Shigella bacteria, are required to cause bacillary dysentery. This is remarkable when one considers that the inoculum must pass through the stomach, with a pH of less than 3.0 in order to reach the intestines. In contrast the infective dose of Salmonella species and Vibrio cholora is more than 100,000 bacteria. We have shown that Shigella is able to survive exposure to pH 2.5 for several hours under conditions in which Salmonella species are readily killed. We had previously shown that rpoS, a stationary phase sigma factor, was required for expression of acid resistance. Recently we have identified two rpoS regulated genes, gadC and hdeA, which mediate acid resistance. One of these genes is gadC, a previously unknown gene which encodes a protein with significant homology to a number of inner membrane amino acid antiporters. We have found that neither hdeA nor gadC are present in Salmonella species which may explain this organism's high infective dose. Introduction of these genes into Salmonella could lead to the development of better oral vaccine strains. We have also investigated the acid sensitivity of clinical isolates of an emerging pathogen enterohemorrhagic Escherichia coli (EHEC) found that some of these strains are acid sensitive due to defective rpoS alleles. This suggests that there may be significant differences in the virulence of EHEC strains. Although many enteric pathogens infect a number of host species, Shigella species and some species of Salmonella cause disease only in a single host species. We have used the chicken-specific Salmonella gallinarum, the human specific Salmonella typhi and mouse-specific Salmonella typhimurium to explore the basis of host specificity. Although S. gallinarum does not infect mice through oral administration, we have cloned a sement of DNA from the S. typhimurium virulence plasmid which enhances the ability of S. gallinarum to colonize the mouse.